Yoshimu Tanaka

Plasma lnterleukin-6 Levels in Continuous Ambulatory Peritoneal Dialysis and Hemodialysis Patients

Plasma levels of interleukin-6 (IL-6), a cytokine known to be involved in lymphocyte activation and in inflammation, were studied in 10 normal volunteers, 21 continuous ambulatory peritoneal dialysis

CYFRA 21-1 and ProGRP, tumor markers of lung cancer, are elevated in chronic renal failure patients.

Abstract Serum levels of CYFRA 21‐1(cytokeratin‐19 fragment) and ProGRP (pro‐gastrin‐releasing peptide), the new prognostic markers of lung cancer, were measured by ELISA (enzyme‐linked immunoadsorbent assay) in 27 (for CYFRA 21‐1; male 13, female 14; age 54 ± 17 years) or 22 (for ProGRP; male 9, female 13; age 59 ± 18 years) patients with various serum creatinine levels, 42 haemodialysis (HD) patients (male 24, female 18; age 59 ± 14 years) and 30 continuous ambulatory peritoneal dialysis (CAPD) patients (male 18, female 12; age 48 ± 9 years). All the patients were without clinical and radiological signs of lung cancer. Positive correlations were found between serum creatinine and serum CYFRA 21‐1 and ProGRP levels. Serum levels of CYFRA 21‐1 were above the cutoff limit (3.5 ng/mL) in 57% of HD patients (mean 4.07 ± 1.56 ng/mL) and in 73% of CAPD patients (mean 4.87 ± 1.56 ng/mL). Serum levels of ProGRP were above the cutoff limit (46.0 pg/mL) in 90% of HD patients (mean 107.0 ± 59.4 pg/mL) and in 93% of CAPD patients (mean 112.4 ± 4.5 pg/mL). Our data indicate that evaluation of renal function is essential when the measurement of these tumor markers is to be applied as one of the diagnostic tools of lung cancer.

Niceritrol reduces plasma lipoprotein(a) levels in patients undergoing maintenance hemodialysis

Lp(a) is an LDL-like lipoprotein carrying the apoprotein(a) glycoprotein and has recently been recognized to be an independent risk factor for coronary heart disease. We studied plasma Lp(a) levels in 40 patients undergoing maintenance hemodialysis (24 male, 16 female; aged 16-83 years). Fasting plasma Lp(a) levels were measured by an enzyme-linked immunosorbent assay. The median value of plasma Lp(a) concentrations in hemodialysis patients was significantly higher than that of the normal volunteers (26.0 +/- 2.7 vs. 10.8 +/- 3.7 mg/dL, p < .05). Lp(a) levels did not correlate with age, duration of hemodialysis, total cholesterol, triglyceride, HDL cholesterol, or LDL cholesterol. The 11 patients whose plasma Lp(a) concentrations exceeded 20 mg/dL received niceritrol, a prodrug of nicotinic acid, at a dosage of 500 mg t.i.d. for 4 weeks. The plasma Lp(a) levels were significantly lower after 4 weeks of treatment (38.3 +/- 4.2 vs. 31.5 +/- 3.2 mg/dL, p < .01).

Calcium-activated, phospholipid-dependent protein kinase in cultured rat mesangial cells.

The analysis of the 100000 × g supernatant fraction of cultured rat glomerular mesangial cells with DEAE‐cellulose ion‐exchange chromatography revealed a large peak showing the activity of a protein kinase (protein kinase C) which depended on phospholipid and diolein as well as Ca2+ Furthermore, it was shown that angiotensin II (AII) (10−6 M) induced rapid hydrolysis of phosphatidylinositol 4,5‐bisphosphate, leading to production of diacylglycerol rich in arachidonic acid, in the cultured rat mesangial cells. These results suggest that activation of protein kinase C resulting from enhancement of phosphoinositide metabolism may be important as an intracellular regulatory mechanism of AII upon cultured mesangial cells.

Elevated Serum Pepsinogens in Chronic Renal Failure Patients

Human pepsinogens, the precursors of pepsin, originating from the stomach mucosa, are classified into two biochemically distinct groups, namely pepsinogen I (PG I) and pepsinogen II (PG II). We studied the serum levels of PG I and II in 51 normal volunteers, 23 chronic glomerulonephritis patients, 21 continuous ambulatory peritoneal dialysis (CAPD) patients and 40 hemodialysis patients. Serum pepsinogen levels were measured with a competitive binding double antibody radioimmunoassay. In the group of chronic glomerulonephritis patients, a positive correlation between the serum creatinine and the pepsinogen levels were found. The serum pepsinogen levels were remarkably elevated in CAPD and hemodialysis patients. The median levels of post-hemodialysis PG I (265.4 +/- 165.2 ng/ml) and PG II (41.7 +/- 38.0 ng/ml) were significantly higher than prehemodialysis values (PG I 207.4 +/- 127.5 ng/ml, PG II 29.0 +/- 16.6 ng/ml). Pepsinogen release by isolated gastric glands of guinea pigs was suppressed by guanidinosuccinic acid and was facilitated by calcium. The data suggest that both removal of guanidinosuccinic acid and infusion of calcium during hemodialysis contribute to the raised serum levels of these pepsinogens after hemodialysis.

New Acute Peritoneal Dialysis Technique: Wire-Guide Insertion and Long-Term Indwelling of Peritoneal Catheter

This paper presents the application of wire-guide insertion of peritoneal dialysis catheter. 30 patients who required acute peritoneal dialysis were treated using a total of 37 peritoneal catheters with the wire-guide method. The catheters were left in place as long as possible (periods totalling 644 days in all). The complication of insertion was minor bleeding with blood-tinged dialysate that tended to clear spontaneously in a few days. Leakage occurred in 17 indwelling catheters but did not occur on the days of insertion. There were 3 episodes of clinical peritonitis, so the infection rate was 1 episode every 7 patient-months. This technique is safer and simpler, i.e. the incidence of peritonitis is lower in long-term indwelling catheters, and so it will contribute to the wider and earlier utilization of peritoneal dialysis.

Phosphoinositide turnover enhanced by angiotensin II in isolated rat glomeruli

To clarify the signal transduction mechanism of angiotensin II in renal glomeruli, we studied the effect of the hormone on phospholipid metabolism using isolated rat glomeruli. Stimulation of the glomeruli pulse-chase labeled with [3H]glycerol by angiotensin II caused a rapid (within 15 s) breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) with a concurrent production of 1,2-diacylglycerol. This effect of angiotensin II was in a dose-dependent manner within the range from 10(-12) M to 10(-6) M, and was inhibited by saralasin. Angiotensin II also decreased the 3H radioactivity of PIP slightly only at 15 s and increased that of phosphatidic acid after 15 s, with no significant effect upon the labelings of phosphatidylinositol (PI), phosphatidylcholine (PC) and phosphatidylethanolamine (PE) within 1 min. The change in phospholipid metabolism by angiotensin II was similar when the glomeruli were labeled with [32P]orthophosphate: the decrease in the labeling of PIP2 and the increase in the labeling of phosphatidic acid after 15 s. In addition, 32P labeling of PI increased after 2 min. These results suggest that angiotensin II, after binding to glomerular receptors, induces initial PIP2 hydrolysis to diacylglycerol and subsequent resynthesis of PIP2 through phosphoinositide turnover.

Evaluation of Hemodialysis Efficiency by an Edema Fluid Model

The concentrations of urea, creatinine, and uric acid were measured in edema fluid and plasma during hemodialysis and 18 h after hemodialysis. The concentrations of these solutes in plasma were 15-17% lower than in the edema fluid after hemodialysis. Eighteen hours after hemodialysis, however, the concentrations in plasma were almost the same as those in edema fluid. These data suggest that the removal of these solutes from the extracellular space is delayed during hemodialysis. The plasma concentrations obtained at 18 h after hemodialysis are better indicators of hemodialysis efficiency.

Pharmacokinetics of Denopamine in Hemodialysis Patients

The pharmacokinetics of denopamine on a hemodialysis day and on an interdialysis day was evaluated in 11 hemodialysis patients. Tmax was the only pharmacokinetical parameter that differed significantly between healthy volunteers and hemodialysis patients. It is suggested that denopamine can be administered to hemodialysis both on hemodialysis days and on interdialysis days without dosage adjustments.

Treatment of hemodialysis-induced hypotension with oral droxidopa.

血液透析 (HD) 中の低血圧発作 (HIH) は深刻な合併症である. ドロキシドパ (DOPS) は, 経口投与が可能なnorepinephrine (NE) 前駆アミノ酸で, Shy-Drager症候群などに見られる起立性低血圧に臨床応用されている. 我々はすでに, HD患者においてもDOPSが有効に吸収されNEに変換し, HIHに対して有効例の存在することを報告した. そこで今回, 多施設における初期第II相試験を行い, 用量設定に関しても検討した. 5施設において, 処置を要するHIHを呈した週3回の慢性HD患者34例 (男14例, 糖尿病性腎不全〔DM〕12例) を対象とした. DOPSはHD開始1時間前に200mgから服用させ, 効果に応じて1週毎に100mgずつ, 400mgまで増量し6週継続した. 本試験中透析条件は一定とし, 一定の透析経過記載表を用い, 観察項目, HIHに対する処置を統一した. 全症例の比較でも, 透析中の最低血圧時, 透析終了時, 終了後立位時の血圧がいずれも有意に上昇した. また, HIHに対する補液量, 処置回数も有意に減少した.個々の症例の検討でも, 67.6%に有用性が認められ, 透析中の自覚症状の改善が73.5%に, 透析終了後の改善が64.7%に得られた. 副作用は3例に見られたが, 減量後消失し, DOPSの継続は可能であった. 最終投与量は200mg13例, 300mg7例, 400mg14例で, 400mg群の有用性は200, 300mg群に比べ有意に低値であった. 年齢, 透析期間と有効性には関連はないが, HIHの軽症な患者, HD前収縮期血圧の低い患者に有用率が高い. また, DM患者の有用率は慢性糸球体腎炎患者に比べ有意に低値であったが, 補液量, 処置回数は, 両者とも有意に減少した. HD前NE濃度は有用性と関連が認められなかった. 以上, HIHを呈する慢性HD患者の約2/3の症例にDOPSの有用性を確認した.